迷迭香酸对大鼠海马内注射海藻酸后细胞凋亡及神经元型一氧化氮合酶免疫反应性的影响
The Effect of Rosmarinic Acid on Apoptosis and nNOS Immunoreactivity Following Intrahippocampal Kainic Acid Injections in Rats.
作者信息
Khamse Safoura, Sadr Seyed Shahabeddin, Roghani Mehrdad, Rashvand Mina, Mohammadian Maryam, Marefati Narges, Harati Elham, Ebrahimi Fatemeh
机构信息
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
出版信息
Basic Clin Neurosci. 2020 Jan-Feb;11(1):41-48. doi: 10.32598/bcn.9.10.340. Epub 2020 Jan 1.
INTRODUCTION
Kainic Acid (KA) is an ionotropic glutamate receptor agonist. KA can induce neuronal overactivity and excitotoxicity. Rosmarinic Acid (RA) is a natural polyphenolic compound with antioxidant, anti-apoptotic, anti-neurodegenerative, and anti-inflammatory properties. This study aimed to assess the effect of RA on apoptosis, nNOS-positive neurons number, as well as Mitogen-Activated Protein Kinase (MAPK) and Cyclooxygenase-2 (COX-2) immunoreactivity, following intrahippocampal Kainic acid injection in rats.
METHODS
The study rats were randomly assigned to three groups of sham, KA (KA was injected into the right side of the hippocampus) and KA+RA (a dose of 10 mg/kg/day through a gavage needle for one week before KA injection). Then, histopathological changes, including apoptosis [Terminal Deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay], nNOS-positive neurons number, as well as COX-2 and MAPK immunoreactivity were evaluated in the hippocampus.
RESULTS
In the RA pretreated group, nNOS-positive neurons and TUNEL-positive cells were significantly reduced compared to the KA group (P<0.05). COX-2and MAPK immunoreactivity demonstrated no significant changes compared to the KA group. They indicated a significant higher reactivity for COX-2 (P<0.01) and MAPK (P<0.005) versus the sham group.
CONCLUSION
RA had neuroprotective effects, compared to KA, through reduced apoptosis and nNOS-positive neurons, but not MAPK and COX-2.
引言
海藻酸（KA）是一种离子型谷氨酸受体激动剂。KA可诱导神经元过度活动和兴奋性毒性。迷迭香酸（RA）是一种天然多酚化合物，具有抗氧化、抗凋亡、抗神经退行性变和抗炎特性。本研究旨在评估RA对大鼠海马内注射海藻酸后细胞凋亡、nNOS阳性神经元数量以及丝裂原活化蛋白激酶（MAPK）和环氧化酶-2（COX-2）免疫反应性的影响。
方法
将研究大鼠随机分为三组：假手术组、KA组（将KA注射到海马右侧）和KA+RA组（在注射KA前一周通过灌胃针给予10mg/kg/天的剂量，持续一周）。然后，评估海马中的组织病理学变化，包括细胞凋亡[末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记（TUNEL）测定]、nNOS阳性神经元数量以及COX-2和MAPK免疫反应性。
结果
与KA组相比，RA预处理组的nNOS阳性神经元和TUNEL阳性细胞显著减少（P<0.05）。与KA组相比，COX-2和MAPK免疫反应性无显著变化。与假手术组相比，它们显示出COX-2（P<0.01）和MAPK（P<0.005）的反应性显著更高。
结论
与KA相比，RA通过减少细胞凋亡和nNOS阳性神经元发挥神经保护作用，但对MAPK和COX-2无作用。
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